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EndNote groups citations into "libraries" with the file extension *.enl and a corresponding *.data folder.

There are several ways to add a reference to a library: manually, or by exporting, importing, copying from another EndNote library, or connecting from EndNote. The program presents the user with a window containing a dropdown menu from which to select the type of reference they require (e.g., book, congressional legislation, film, newspaper article, etc.), and fields ranging from the general (author, title, year) to those specific to the kind of reference (abstract, author, ISBN, running time, etc.)

Most bibliographic databases allow users to export references to their EndNote libraries. This enables the user to select multiple citations and saves the user from having to manually enter the citation information and the abstracts. Some databases (e.g., PubMed) requires the user to select citations, select a specific format, and save them as .txt files. The user can then import the citations into the EndNote software. It is also possible to search library catalogs and free databases, such as PubMed, from within the EndNote software program itself.

If the user fills out the necessary fields, EndNote can automatically format the citation into any of over 2,000 different styles the user chooses. For example, listed below are some citations from Gray's Anatomy using several different styles:

In Windows, EndNote creates a file with an *.enl extension, along with a *.data folder containing various MySQL files with *.myi and *.myd extensions. EndNote can be installed so that its features, like Cite While You WriteTM, appear in the Tools menu of Microsoft Word and OpenOffice.org Writer.

EndNote can export citation libraries as HTML, plain text, Rich Text Format, or XML. From version X.7.2, one library can be shared with up to 14 other EndNote users. The data is synchronized via the EndNote cloud service, with everybody having full write access to the library.[2]

EndNote can also organize PDFs on the user's hard drive (or full text on the web) through links to files or by inserting copies of PDFs. It is also possible to save a single image, document, Excel spreadsheet, or other file type to each reference in an EndNote library. Starting from EndNote X version 1.0.1, formatting support for OpenDocument files (ODT) using the Format Paper command is supported.

In September 2008, Thomson Reuters, the owners of EndNote, sued the Commonwealth of Virginia for $10 million and requested an injunction against competing reference management software.[3][4]George Mason University's Center for History and New Media had developed Zotero, a free/open source extension to Mozilla Firefox. Thomson Reuters alleges that the Zotero developers reverse engineered and/or decompiled EndNote, that Zotero can transform proprietary EndNote citation style files (.ens) to the open Citation Style Language format, that they host files converted in this manner, and that they abuse the "EndNote" trademark in describing this feature. Thomson Reuters claims that this is violation of the site license agreement. They also added a restrictive click-thru license to their styles download web site.[4] George Mason University responded that it would not renew its site license for EndNote, that "anything created by users of Zotero belongs to those users, and that it should be as easy as possible for Zotero users to move to and from the software as they wish, without friction."[5] The journal Nature editorialized that "the virtues of interoperability and easy data-sharing among researchers are worth restating. Imagine if Microsoft Word or Excel files could be opened and saved only in these proprietary formats, for example. It would be impossible for OpenOffice and other such software to read and save these files using open standards — as they can legally do."[6]

EndNote X7 for Windows, released 20 May 2013; Compatible with Microsoft Word 2013.

EndNote X6 for Windows, released 6 August 2012; EndNote X6 for Mac, released Q4 2012, compatible with OS X 10.8.

EndNote X5 for Mac, released September 2011, introduced official compatibility with OS X 10.7 Lion.[10]

EndNote X5 for Windows, released 21 June 2011. Compatible with Microsoft Word 2010[11]

EndNote X4 for Mac, released 23 August 2010.[12] Introduced official compatibility with Mac OS X 10.6 Snow Leopard. Initially not compatible with Microsoft Office 2011, a compatibility update was subsequently made available on the EndNote website.[13]

EndNote X4 for Windows, released 15 June 2010.[14] Introduced official compatibility with Microsoft Windows 7.[15] Introduced official compatibility with Microsoft Word 2010 (required an update via Help -> Program Updates, or directly from the Endnote website).[13]

EndNote X3 for Mac, released 26 August 2009.[16] Not compatible with Microsoft Word 2011.[13] EndNote X3 and later are not supported on systems running Mac OS X 10.4 Tiger.[17]

EndNote X3 for Windows, released 17 June 2009.[18] Not compatible with Microsoft Word 2010;[13] Word 2010 cannot be started without disabling the EndNote Addin.

EndNote X2 for Windows, released 11 June 2008.[20] The "Cite While You Write" feature in EndNote X2 was originally not compatible with 64-bit versions of Windows, but a patch can fix this issue.[21] Last update: Version 12.0.4 (build 4459).

EndNote X1 for Mac, released 21 August 2007.[22] The Cite While You Write feature of EndNote X1 for Mac OS was originally only compatible with Word 10.1.2-10.1.6 and Word 2004. Due to changes in the way third party addins were supported in Word 2008, Cite While You Write was not natively compatible with Word 2008. A patch was released on June 26, 2008 that restored cite while you write functionality to Word 2008.[23]

EndNote X1 for Windows, released 20 August 2007.[24] EndNote X1 and later are compatible with Windows Vista.[15]

EndNote X for Mac, released 25 August 2006.[25] EndNote X and later are "Universal applications" that execute natively on both PPC and Intel-based Macs.[26] Introduced compatibility with Mac OS X 10.5 Leopard.[10] EndNote libraries that have been opened and used with EndNote version X or greater should not be subsequently used with an EndNote version earlier than version X.[27]

EndNote X for Windows, released 9 June 2006.[28] EndNote libraries that have been opened and used with EndNote version X or greater should not be subsequently used with an EndNote version earlier than version X.[27]

EndNote 9 for Mac, released 29 August 2005.[29] Introduced compatibility with Mac OS X 10.4 Tiger.[17] Due to major compatibility issues, it is not recommend to run EndNote 9 or earlier on OS X 10.5 Leopard.[10]

EndNote 7 for Mac, released 26 August 2003.[33] Not certified compatible with OS X 10.3 Panther (users can install and run EndNote 7 on a Panther system, but there are some minor compatibility issues).[34]

EndNote 6 for Mac, released 5 August 2002.[36] Not certified compatible with OS X 10.3 Panther (it is possible to install and run EndNote 6 on a Panther system, but there are some minor compatibility issues).[34]